Trial Outcomes & Findings for Multiple Dose Pharmacokinetics Depot Buprenorphine in Opioid-Dependent Subjects (NCT NCT01738503)

Last Updated: 2018-02-23

Results Overview

TEAE=any untoward medical occurrence that develops or worsens in severity after dispensation of the study drug and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= a marked limitation in activity. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent one of the outcomes listed in this definition. A serious AE (SAE) is defined as any AE occurring at any dose that results in any of the following outcomes: death; lifethreatening AE; hospitalization or prolongation of existing hospitalization; a persistent or significant disability/incapacit

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

124 participants

Primary outcome timeframe

Days -14 to -1 (Subutex treatment), Days 1-316 (RBP-6000 treatment)

Results posted on

2018-02-23

Participant Flow

A total of 395 subjects provided informed consent to participate in the main study and underwent screening procedures. Of these 395 subjects, 124 received study treatment.

Participant milestones

Participant milestones
Measure	SUBUTEX Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL. Those who did not complete this period, did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 3 (24 mg) RBP-6000: 200 mg Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Induction/Stabilization (Days -14 to -1) STARTED	124	0	0	0	0	0	0
Induction/Stabilization (Days -14 to -1) COMPLETED	89	0	0	0	0	0	0
Induction/Stabilization (Days -14 to -1) NOT COMPLETED	35	0	0	0	0	0	0
Treatment Period STARTED	0	15	15	15	15	15	14
Treatment Period COMPLETED	0	10	10	9	7	9	6
Treatment Period NOT COMPLETED	0	5	5	6	8	6	8
PET Imaging Sub-study STARTED	0	0	0	0	0	3	2
PET Imaging Sub-study COMPLETED	0	0	0	0	0	1	1
PET Imaging Sub-study NOT COMPLETED	0	0	0	0	0	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	SUBUTEX Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL. Those who did not complete this period, did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 3 (24 mg) RBP-6000: 200 mg Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Induction/Stabilization (Days -14 to -1) Other	35	0	0	0	0	0	0
Treatment Period Adverse Event	0	1	0	1	2	2	2
Treatment Period Lost to Follow-up	0	0	3	4	1	1	5
Treatment Period Withdrawal by Subject	0	1	0	1	1	1	1
Treatment Period Protocol Violation	0	3	1	0	4	2	0
Treatment Period Other	0	0	1	0	0	0	0
PET Imaging Sub-study Adverse Event	0	0	0	0	0	1	0
PET Imaging Sub-study Scheduling issues with imaging facility	0	0	0	0	0	1	1

Baseline Characteristics

Missing participants reported no use

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg n=14 Participants Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Total n=89 Participants Total of all reporting groups
Age, Continuous	36.5 years STANDARD_DEVIATION 11.36 • n=15 Participants	31.1 years STANDARD_DEVIATION 11.14 • n=15 Participants	30.1 years STANDARD_DEVIATION 11.21 • n=15 Participants	36.1 years STANDARD_DEVIATION 14.87 • n=15 Participants	36.2 years STANDARD_DEVIATION 12.85 • n=15 Participants	32.9 years STANDARD_DEVIATION 11.00 • n=14 Participants	33.8 years STANDARD_DEVIATION 12.10 • n=89 Participants
Sex: Female, Male Female	3 Participants n=15 Participants	5 Participants n=15 Participants	5 Participants n=15 Participants	6 Participants n=15 Participants	6 Participants n=15 Participants	4 Participants n=14 Participants	29 Participants n=89 Participants
Sex: Female, Male Male	12 Participants n=15 Participants	10 Participants n=15 Participants	10 Participants n=15 Participants	9 Participants n=15 Participants	9 Participants n=15 Participants	10 Participants n=14 Participants	60 Participants n=89 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=14 Participants	0 Participants n=89 Participants
Race (NIH/OMB) Asian	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=14 Participants	0 Participants n=89 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=14 Participants	0 Participants n=89 Participants
Race (NIH/OMB) Black or African American	7 Participants n=15 Participants	3 Participants n=15 Participants	3 Participants n=15 Participants	5 Participants n=15 Participants	5 Participants n=15 Participants	3 Participants n=14 Participants	26 Participants n=89 Participants
Race (NIH/OMB) White	8 Participants n=15 Participants	11 Participants n=15 Participants	12 Participants n=15 Participants	10 Participants n=15 Participants	10 Participants n=15 Participants	11 Participants n=14 Participants	62 Participants n=89 Participants
Race (NIH/OMB) More than one race	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=14 Participants	0 Participants n=89 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=15 Participants	1 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=14 Participants	1 Participants n=89 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=15 Participants	1 Participants n=15 Participants	0 Participants n=15 Participants	1 Participants n=15 Participants	1 Participants n=15 Participants	1 Participants n=14 Participants	4 Participants n=89 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	15 Participants n=15 Participants	14 Participants n=15 Participants	15 Participants n=15 Participants	14 Participants n=15 Participants	14 Participants n=15 Participants	13 Participants n=14 Participants	85 Participants n=89 Participants
Weight	71.12 kg STANDARD_DEVIATION 12.929 • n=15 Participants	73.71 kg STANDARD_DEVIATION 10.411 • n=15 Participants	68.08 kg STANDARD_DEVIATION 9.900 • n=15 Participants	74.43 kg STANDARD_DEVIATION 15.995 • n=15 Participants	73.16 kg STANDARD_DEVIATION 12.753 • n=15 Participants	74.64 kg STANDARD_DEVIATION 16.825 • n=14 Participants	72.50 kg STANDARD_DEVIATION 13.159 • n=89 Participants
Height	173.41 cm STANDARD_DEVIATION 8.514 • n=15 Participants	172.87 cm STANDARD_DEVIATION 8.532 • n=15 Participants	170.50 cm STANDARD_DEVIATION 11.738 • n=15 Participants	171.17 cm STANDARD_DEVIATION 8.701 • n=15 Participants	168.71 cm STANDARD_DEVIATION 10.963 • n=15 Participants	170.64 cm STANDARD_DEVIATION 11.469 • n=14 Participants	171.22 cm STANDARD_DEVIATION 9.906 • n=89 Participants
Body Mass Index	23.55 kg/m^2 STANDARD_DEVIATION 3.084 • n=15 Participants	24.67 kg/m^2 STANDARD_DEVIATION 3.239 • n=15 Participants	23.39 kg/m^2 STANDARD_DEVIATION 2.298 • n=15 Participants	25.26 kg/m^2 STANDARD_DEVIATION 4.295 • n=15 Participants	25.67 kg/m^2 STANDARD_DEVIATION 3.635 • n=15 Participants	25.36 kg/m^2 STANDARD_DEVIATION 3.355 • n=14 Participants	24.64 kg/m^2 STANDARD_DEVIATION 3.394 • n=89 Participants
Other Opioid Use	6.75 years STANDARD_DEVIATION 5.545 • n=12 Participants • Missing participants reported no use	6.18 years STANDARD_DEVIATION 4.191 • n=11 Participants • Missing participants reported no use	4.17 years STANDARD_DEVIATION 2.887 • n=12 Participants • Missing participants reported no use	5.27 years STANDARD_DEVIATION 3.927 • n=11 Participants • Missing participants reported no use	8.36 years STANDARD_DEVIATION 9.770 • n=11 Participants • Missing participants reported no use	6.30 years STANDARD_DEVIATION 8.693 • n=10 Participants • Missing participants reported no use	6.15 years STANDARD_DEVIATION 6.165 • n=67 Participants • Missing participants reported no use
Heroin Use	11.25 years STANDARD_DEVIATION 10.463 • n=12 Participants • Missing participants reported no use	9.78 years STANDARD_DEVIATION 11.454 • n=9 Participants • Missing participants reported no use	5.00 years STANDARD_DEVIATION 5.604 • n=11 Participants • Missing participants reported no use	11.64 years STANDARD_DEVIATION 12.549 • n=14 Participants • Missing participants reported no use	10.70 years STANDARD_DEVIATION 7.987 • n=10 Participants • Missing participants reported no use	8.56 years STANDARD_DEVIATION 12.471 • n=9 Participants • Missing participants reported no use	9.62 years STANDARD_DEVIATION 10.292 • n=65 Participants • Missing participants reported no use
Smoking History (Nicotine Use)	15.14 years STANDARD_DEVIATION 10.596 • n=14 Participants • Missing participants reported no use	10.64 years STANDARD_DEVIATION 5.387 • n=14 Participants • Missing participants reported no use	9.57 years STANDARD_DEVIATION 8.225 • n=14 Participants • Missing participants reported no use	19.83 years STANDARD_DEVIATION 14.282 • n=12 Participants • Missing participants reported no use	20.07 years STANDARD_DEVIATION 11.526 • n=14 Participants • Missing participants reported no use	17.31 years STANDARD_DEVIATION 13.054 • n=13 Participants • Missing participants reported no use	15.30 years STANDARD_DEVIATION 11.243 • n=81 Participants • Missing participants reported no use

PRIMARY outcome

Timeframe: Days -14 to -1 (Subutex treatment), Days 1-316 (RBP-6000 treatment)

Population: Safety analysis group

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=35 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg n=14 Participants Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Participants With Treatment-Emergent Adverse Events (TEAEs) >=1 TEAE	24 Participants	15 Participants	15 Participants	15 Participants	15 Participants	15 Participants	14 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) >=1 TEAE related to study drug	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) >=1 Severe TEAE	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) Deaths	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) >=1 SAE other than death	0 Participants	0 Participants	2 Participants	1 Participants	1 Participants	2 Participants	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) Withdrew from study due to a TEAE	0 Participants	1 Participants	0 Participants	1 Participants	2 Participants	2 Participants	2 Participants

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

Population: The PK analysis population was defined as any subject in Groups 1 - 6 who received a dose of RBP-6000 or at least 1 dose of SUBUTEX SL tablet and had an adequate number of PK samples collected to derive PK parameters.

% Fluctuation was defined as the degree of fluctuation of buprenorphine plasma concentrations calculated as (Cmax-Cmin)/Cavg\*100, expressed as a percentage. Cmax=maximum plasma concentration Cmin=minimum plasma concentration Cavg = average plasma concentration Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Buprenorphine PK: % Fluctuation Sublingual Period	256.993 % of average concentration Standard Deviation 68.4944	272.702 % of average concentration Standard Deviation 62.1424	233.978 % of average concentration Standard Deviation 84.1776	268.690 % of average concentration Standard Deviation 54.5116	227.874 % of average concentration Standard Deviation 69.1437	245.513 % of average concentration Standard Deviation 61.2524	—
Buprenorphine PK: % Fluctuation Plateau: Injection 1	213.664 % of average concentration Standard Deviation 50.7221	175.068 % of average concentration Standard Deviation 69.0037	168.963 % of average concentration Standard Deviation 31.8302	140.924 % of average concentration Standard Deviation 39.3779	135.433 % of average concentration Standard Deviation 31.4609	107.909 % of average concentration Standard Deviation 33.9246	—
Buprenorphine PK: % Fluctuation Plateau: Injection 4	68.333 % of average concentration Standard Deviation 16.8729	63.611 % of average concentration Standard Deviation 27.6839	42.699 % of average concentration Standard Deviation 5.6645	41.275 % of average concentration Standard Deviation 14.1786	47.282 % of average concentration Standard Deviation 21.0395	53.383 % of average concentration Standard Deviation 20.9467	—
Buprenorphine PK: % Fluctuation Plateau: Injection 6	—	—	—	—	22.597 % of average concentration	31.376 % of average concentration	—
Buprenorphine PK: % Fluctuation Overall: Injection 1	315.777 % of average concentration Standard Deviation 106.6237	234.098 % of average concentration Standard Deviation 60.7481	234.598 % of average concentration Standard Deviation 66.4979	213.254 % of average concentration Standard Deviation 68.1754	206.691 % of average concentration Standard Deviation 79.9858	220.854 % of average concentration Standard Deviation 70.3346	—
Buprenorphine PK: % Fluctuation Overall: Injection 4	152.755 % of average concentration Standard Deviation 75.3194	95.140 % of average concentration Standard Deviation 20.9504	75.633 % of average concentration Standard Deviation 17.3765	77.067 % of average concentration Standard Deviation 21.4559	75.202 % of average concentration Standard Deviation 28.4598	83.695 % of average concentration Standard Deviation 12.8165	—
Buprenorphine PK: % Fluctuation Overall: Injection 6	—	—	—	—	54.789 % of average concentration Standard Deviation 1.6355	—	—

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

AUC calculated using the linear trapezoidal rule and requiring a minimum of 5 data points for each time range. Results are reported across four timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading at hours 0-24. * Initial Burst Parameters (Days 1-2 relative to RBP-6000 injections 1, 4 and 6) at hours 0-48 * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) at hours 48-672 * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) at hours 0-24, hours 0-672 The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Sublingual Period (0-24 hours)	28.452 hr*ng/mL Standard Deviation 7.9415	40.971 hr*ng/mL Standard Deviation 12.6823	63.019 hr*ng/mL Standard Deviation 16.4068	30.029 hr*ng/mL Standard Deviation 12.8676	46.681 hr*ng/mL Standard Deviation 11.8403	46.628 hr*ng/mL Standard Deviation 23.2554	—
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Initial Burst: Injection 1 (0-48 hours)	46.855 hr*ng/mL Standard Deviation 11.5533	72.453 hr*ng/mL Standard Deviation 25.4451	109.029 hr*ng/mL Standard Deviation 30.2598	62.395 hr*ng/mL Standard Deviation 20.3054	104.868 hr*ng/mL Standard Deviation 22.6943	164.511 hr*ng/mL Standard Deviation 47.8237	—
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Initial Burst: Injection 4 (0-48 hours)	69.845 hr*ng/mL Standard Deviation 24.4947	113.347 hr*ng/mL Standard Deviation 29.7760	185.535 hr*ng/mL Standard Deviation 48.2330	98.566 hr*ng/mL Standard Deviation 17.8092	172.421 hr*ng/mL Standard Deviation 29.3259	381.729 hr*ng/mL Standard Deviation 81.4365	—
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Initial Burst: Injection 6 (0-48 hours)	—	—	—	—	216.540 hr*ng/mL Standard Deviation 48.7904	320.159 hr*ng/mL	—
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Plateau: Injection 1 (2-28 days)	208.013 hr*ng/mL Standard Deviation 43.2691	395.450 hr*ng/mL Standard Deviation 115.3659	541.226 hr*ng/mL Standard Deviation 193.6220	368.925 hr*ng/mL Standard Deviation 137.2231	648.344 hr*ng/mL Standard Deviation 217.2051	926.110 hr*ng/mL Standard Deviation 285.6452	—
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Plateau: Injection 4 (2-28 days)	596.568 hr*ng/mL Standard Deviation 227.2414	1142.046 hr*ng/mL Standard Deviation 380.1915	1807.403 hr*ng/mL Standard Deviation 441.0377	1073.201 hr*ng/mL Standard Deviation 240.7532	1859.204 hr*ng/mL Standard Deviation 477.7799	3426.313 hr*ng/mL Standard Deviation 672.5864	—
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Plateau: Injection 6 (2-28 days)	—	—	—	—	2209.11 hr*ng/mL	3460.459 hr*ng/mL	—
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Overall: Injection 1 (0-24 hours)	24.922 hr*ng/mL Standard Deviation 6.4450	36.981 hr*ng/mL Standard Deviation 14.3565	55.291 hr*ng/mL Standard Deviation 17.0179	31.747 hr*ng/mL Standard Deviation 13.2180	50.034 hr*ng/mL Standard Deviation 11.4899	85.090 hr*ng/mL Standard Deviation 28.7163	—
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Overall: Injection 1 (0-28 days)	246.650 hr*ng/mL Standard Deviation 54.9881	461.366 hr*ng/mL Standard Deviation 142.2166	642.010 hr*ng/mL Standard Deviation 228.0284	413.438 hr*ng/mL Standard Deviation 133.0365	756.053 hr*ng/mL Standard Deviation 233.8099	1268.012 hr*ng/mL Standard Deviation 389.6719	—
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Overall: Injection 4 (0-24 hours)	35.250 hr*ng/mL Standard Deviation 14.5405	56.231 hr*ng/mL Standard Deviation 15.6411	91.197 hr*ng/mL Standard Deviation 27.4005	47.633 hr*ng/mL Standard Deviation 9.6147	81.417 hr*ng/mL Standard Deviation 18.3829	178.109 hr*ng/mL Standard Deviation 43.2176	—
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Overall: Injection 4 (0-28 days)	667.611 hr*ng/mL Standard Deviation 254.2712	1272.047 hr*ng/mL Standard Deviation 434.1013	1932.068 hr*ng/mL Standard Deviation 455.1540	1275.098 hr*ng/mL Standard Deviation 252.8500	2051.989 hr*ng/mL Standard Deviation 466.6935	3230.873 hr*ng/mL Standard Deviation 430.6718	—
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Overall: Injection 6 (0-24 hours)	—	—	—	—	—	155.779 hr*ng/mL	—
Buprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Overall: Injection 6 (0-28 days)	—	—	—	—	2585.976 hr*ng/mL Standard Deviation 276.6695	—	—

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

Cavg was defined as the AUC (timeframe)/timeframe. For example, the sublingual steady-state Cavg reading on Day -1 = AUC0-24/ 24 hours Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Buprenorphine PK: Average Plasma Concentration (Cavg) Sublingual Period	1.186 ng/mL Standard Deviation 0.3309	1.707 ng/mL Standard Deviation 0.5284	2.626 ng/mL Standard Deviation 0.6836	1.251 ng/mL Standard Deviation 0.5362	1.945 ng/mL Standard Deviation 0.4933	1.943 ng/mL Standard Deviation 0.9690	—
Buprenorphine PK: Average Plasma Concentration (Cavg) Plateau: Injection 1	0.333 ng/mL Standard Deviation 0.0693	0.634 ng/mL Standard Deviation 0.1849	0.867 ng/mL Standard Deviation 0.3103	0.591 ng/mL Standard Deviation 0.2199	1.039 ng/mL Standard Deviation 0.3481	1.484 ng/mL Standard Deviation 0.4578	—
Buprenorphine PK: Average Plasma Concentration (Cavg) Plateau: Injection 4	0.954 ng/mL Standard Deviation 0.3642	1.830 ng/mL Standard Deviation 0.6093	2.896 ng/mL Standard Deviation 0.7068	1.720 ng/mL Standard Deviation 0.3858	2.979 ng/mL Standard Deviation 0.7657	5.491 ng/mL Standard Deviation 1.0779	—
Buprenorphine PK: Average Plasma Concentration (Cavg) Plateau: Injection 6	—	—	—	—	3.540 ng/mL	5.546 ng/mL	—
Buprenorphine PK: Average Plasma Concentration (Cavg) Overall: Injection 1	0.367 ng/mL Standard Deviation 0.0818	0.687 ng/mL Standard Deviation 0.2116	0.955 ng/mL Standard Deviation 0.3393	0.615 ng/mL Standard Deviation 0.1980	1.125 ng/mL Standard Deviation 0.3331	1.887 ng/mL Standard Deviation 0.5799	—
Buprenorphine PK: Average Plasma Concentration (Cavg) Overall: Injection 4	0.993 ng/mL Standard Deviation 0.3784	1.893 ng/mL Standard Deviation 0.6460	2.875 ng/mL Standard Deviation 0.6773	1.897 ng/mL Standard Deviation 0.3763	3.054 ng/mL Standard Deviation 0.6945	4.808 ng/mL Standard Deviation 0.6409	—
Buprenorphine PK: Average Plasma Concentration (Cavg) Overall: Injection 6	—	—	—	—	3.848 ng/mL Standard Deviation 0.4117	—	—

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

Maximum observed plasma concentration, determined directly from individual concentration time data. Results are reported across four timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading at hours 0-24. * Initial Burst Parameters (Days 1-2 relative to RBP-6000 injections 1, 4 and 6) at hours 0-48 * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) at hours 48-672 * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Sublingual Period (0-24 hours)	3.521 ng/mL Standard Deviation 1.0407	5.350 ng/mL Standard Deviation 1.7340	7.571 ng/mL Standard Deviation 3.0928	3.964 ng/mL Standard Deviation 1.9131	5.260 ng/mL Standard Deviation 1.5595	5.813 ng/mL Standard Deviation 3.4264	—
Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Initial Burst: Injection 1 (0-48 hours)	1.352 ng/mL Standard Deviation 0.4641	1.916 ng/mL Standard Deviation 0.6773	2.755 ng/mL Standard Deviation 0.7630	1.686 ng/mL Standard Deviation 0.6200	2.861 ng/mL Standard Deviation 0.7136	4.817 ng/mL Standard Deviation 1.4337	—
Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Initial Burst: Injection 4 (0-48 hours)	2.085 ng/mL Standard Deviation 1.4381	2.958 ng/mL Standard Deviation 0.9624	4.526 ng/mL Standard Deviation 1.3078	2.549 ng/mL Standard Deviation 0.4797	4.404 ng/mL Standard Deviation 0.9231	9.637 ng/mL Standard Deviation 2.3409	—
Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Initial Burst: Injection 6 (0-48 hours)	—	—	—	—	5.015 ng/mL Standard Deviation 0.8980	7.140 ng/mL	—
Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Plateau: Injection 1 (2-28 days)	0.853 ng/mL Standard Deviation 0.2687	1.518 ng/mL Standard Deviation 0.8167	2.018 ng/mL Standard Deviation 0.6205	1.174 ng/mL Standard Deviation 0.3432	2.112 ng/mL Standard Deviation 0.6935	2.975 ng/mL Standard Deviation 0.8839	—
Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Plateau: Injection 4 (2-28 days)	1.384 ng/mL Standard Deviation 0.4767	2.590 ng/mL Standard Deviation 0.8536	3.776 ng/mL Standard Deviation 0.8970	2.211 ng/mL Standard Deviation 0.3824	3.780 ng/mL Standard Deviation 0.6646	7.452 ng/mL Standard Deviation 1.6913	—
Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Plateau: Injection 6 (2-28 days)	—	—	—	—	4.650 ng/mL Standard Deviation 0.8910	6.550 ng/mL	—
Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Overall: Injection 1	1.352 ng/mL Standard Deviation 0.4641	2.023 ng/mL Standard Deviation 0.8251	2.732 ng/mL Standard Deviation 0.7866	1.686 ng/mL Standard Deviation 0.6200	2.861 ng/mL Standard Deviation 0.7136	4.817 ng/mL Standard Deviation 1.4337	—
Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Overall: Injection 4	2.085 ng/mL Standard Deviation 1.4381	3.066 ng/mL Standard Deviation 0.8658	4.526 ng/mL Standard Deviation 1.3078	2.554 ng/mL Standard Deviation 0.4775	4.404 ng/mL Standard Deviation 0.9231	9.637 ng/mL Standard Deviation 2.3409	—
Buprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Overall: Injection 6	—	—	—	—	5.015 ng/mL Standard Deviation 0.8980	7.140 ng/mL	—

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

Minimum observed plasma concentration, determined directly from individual concentration time data. Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading at hours 0-24. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) at hours 48-672 * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Plateau: Injection 1 (2-28 days)	0.206 ng/mL Standard Deviation 0.0556	0.388 ng/mL Standard Deviation 0.1145	0.600 ng/mL Standard Deviation 0.2623	0.388 ng/mL Standard Deviation 0.1554	0.714 ng/mL Standard Deviation 0.2315	1.244 ng/mL Standard Deviation 0.4455	—
Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Overall: Injection 4	0.557 ng/mL Standard Deviation 0.1559	1.263 ng/mL Standard Deviation 0.3574	2.121 ng/mL Standard Deviation 0.4689	1.180 ng/mL Standard Deviation 0.2803	2.256 ng/mL Standard Deviation 0.6472	4.043 ng/mL Standard Deviation 0.6936	—
Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Overall: Injection 6	—	—	—	—	2.910 ng/mL Standard Deviation 0.7354	4.290 ng/mL	—
Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Sublingual Period (0-24 hours)	0.524 ng/mL Standard Deviation 0.2212	0.806 ng/mL Standard Deviation 0.3638	1.385 ng/mL Standard Deviation 0.4806	0.568 ng/mL Standard Deviation 0.2367	0.920 ng/mL Standard Deviation 0.2800	0.927 ng/mL Standard Deviation 0.4667	—
Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Plateau: Injection 4 (2-28 days)	0.791 ng/mL Standard Deviation 0.3017	1.434 ng/mL Standard Deviation 0.3706	2.575 ng/mL Standard Deviation 0.6439	1.552 ng/mL Standard Deviation 0.3448	2.498 ng/mL Standard Deviation 0.7269	4.600 ng/mL Standard Deviation 0.7743	—
Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Plateau: Injection 6 (2-28 days)	—	—	—	—	3.325 ng/mL Standard Deviation 0.1485	4.810 ng/mL	—
Buprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Overall: Injection 1	0.206 ng/mL Standard Deviation 0.0556	0.375 ng/mL Standard Deviation 0.1001	0.589 ng/mL Standard Deviation 0.2522	0.410 ng/mL Standard Deviation 0.1955	0.700 ng/mL Standard Deviation 0.2196	0.836 ng/mL Standard Deviation 0.3756	—

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

The swing of buprenorphine plasma concentrations calculated as (Cmax-Cmin)/Cmin within the dosing interval. Cmax=maximum plasma concentration Cmin=minimum plasma concentration Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Buprenorphine PK: Swing of Plasma Concentrations Plateau: Injection 1	332.132 percentage of Cmin Standard Deviation 127.9638	295.987 percentage of Cmin Standard Deviation 229.0036	253.417 percentage of Cmin Standard Deviation 61.2944	223.388 percentage of Cmin Standard Deviation 94.3116	197.895 percentage of Cmin Standard Deviation 49.3822	147.463 percentage of Cmin Standard Deviation 66.0341	—
Buprenorphine PK: Swing of Plasma Concentrations Plateau: Injection 4	79.731 percentage of Cmin Standard Deviation 27.3175	84.772 percentage of Cmin Standard Deviation 48.3724	47.479 percentage of Cmin Standard Deviation 10.5422	44.874 percentage of Cmin Standard Deviation 18.5656	57.889 percentage of Cmin Standard Deviation 30.3975	61.481 percentage of Cmin Standard Deviation 24.0339	—
Buprenorphine PK: Swing of Plasma Concentrations Overall: Injection 4	279.713 percentage of Cmin Standard Deviation 214.1821	147.264 percentage of Cmin Standard Deviation 48.3533	112.812 percentage of Cmin Standard Deviation 32.8955	120.236 percentage of Cmin Standard Deviation 28.1402	103.271 percentage of Cmin Standard Deviation 43.4914	138.783 percentage of Cmin Standard Deviation 47.6186	—
Buprenorphine PK: Swing of Plasma Concentrations Overall: Injection 6	—	—	—	—	73.993 percentage of Cmin Standard Deviation 13.1102	66.434 percentage of Cmin	—
Buprenorphine PK: Swing of Plasma Concentrations Plateau: Injection 6	—	—	—	—	39.390 percentage of Cmin Standard Deviation 20.5703	36.175 percentage of Cmin	—
Buprenorphine PK: Swing of Plasma Concentrations Overall: Injection 1	586.788 percentage of Cmin Standard Deviation 219.9900	440.102 percentage of Cmin Standard Deviation 200.5223	399.355 percentage of Cmin Standard Deviation 140.2055	350.591 percentage of Cmin Standard Deviation 158.0245	336.666 percentage of Cmin Standard Deviation 149.7124	548.179 percentage of Cmin Standard Deviation 272.0431	—
Buprenorphine PK: Swing of Plasma Concentrations Sublingual Period	656.884 percentage of Cmin Standard Deviation 303.7135	665.742 percentage of Cmin Standard Deviation 314.6530	493.475 percentage of Cmin Standard Deviation 273.1229	597.543 percentage of Cmin Standard Deviation 136.8431	500.322 percentage of Cmin Standard Deviation 183.7474	534.280 percentage of Cmin Standard Deviation 217.8816	—

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

Results are reported across four timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading at hours 0-24. * Initial Burst Parameters (Days 1-2 relative to RBP-6000 injections 1, 4 and 6) at hours 0-48 * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) at hours 48-672 * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) at hours 0-24, hours 0-672 The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Initial Burst: Injection 4 (0-48 hours)	20.000 hours Interval 2.0 to 24.0	20.000 hours Interval 4.0 to 30.07	20.083 hours Interval 8.0 to 30.08	24.000 hours Interval 4.0 to 48.03	24.000 hours Interval 4.0 to 48.0	24.000 hours Interval 4.0 to 36.0	—
Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Plateau: Injection 1 (2-28 days)	48.000 hours Interval 48.0 to 48.0	48.000 hours Interval 48.0 to 457.15	48.000 hours Interval 48.0 to 49.1	48.000 hours Interval 48.0 to 48.07	48.000 hours Interval 48.0 to 48.07	48.000 hours Interval 48.0 to 532.55	—
Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Plateau: Injection 6 (2-28 days)	—	—	—	—	48.000 hours Interval 48.0 to 48.0	48.000 hours Interval 48.0 to 48.0	—
Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Overall: Injection 1 (0-28 days)	20.000 hours Interval 4.0 to 20.05	20.000 hours Interval 4.0 to 414.17	20.000 hours Interval 6.0 to 30.0	20.000 hours Interval 4.0 to 48.0	20.000 hours Interval 6.0 to 48.0	20.000 hours Interval 4.0 to 32.0	—
Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Overall: Injection 6 (0-28 days)	—	—	—	—	24.000 hours Interval 24.0 to 24.0	24.350 hours Interval 24.35 to 24.35	—
Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Sublingual Period (0-24 hours)	2.000 hours Interval 1.0 to 4.0	1.017 hours Interval 0.5 to 2.0	1.117 hours Interval 0.5 to 2.0	2.000 hours Interval 1.0 to 2.0	2.000 hours Interval 0.5 to 2.13	2.000 hours Interval 1.0 to 2.0	—
Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Initial Burst: Injection 1 (0-48 hours)	20.000 hours Interval 4.0 to 20.05	20.000 hours Interval 4.0 to 48.0	20.000 hours Interval 6.0 to 48.0	20.000 hours Interval 4.0 to 48.0	20.000 hours Interval 6.0 to 48.0	20.000 hours Interval 4.0 to 32.0	—
Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Initial Burst: Injection 6 (0-48 hours)	—	—	—	—	24.000 hours Interval 24.0 to 24.0	24.350 hours Interval 24.35 to 24.35	—
Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Plateau: Injection 4 (2-28 days)	48.000 hours Interval 48.0 to 48.07	48.000 hours Interval 48.0 to 315.95	48.000 hours Interval 48.0 to 49.12	48.000 hours Interval 48.0 to 629.07	48.000 hours Interval 48.0 to 485.17	48.000 hours Interval 48.0 to 436.75	—
Buprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Overall: Injection 4 (0-28 days)	20.000 hours Interval 2.0 to 24.0	20.000 hours Interval 12.0 to 315.95	20.083 hours Interval 8.0 to 30.08	24.000 hours Interval 4.0 to 529.83	24.000 hours Interval 4.0 to 48.0	24.000 hours Interval 4.0 to 36.0	—

PRIMARY outcome

Timeframe: Days 1-28, 85-113

Population: PK population of participants with data at both timepoints

Accumulation index in terms of AUC calculated as ratio of AUCtau Injection 4/ AUCtau Injection 1. AUCtau = area under plasma concentration time curve over the dosing interval tau (for SC RBP-6000, tau=28 days).

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=10 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=11 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=9 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=8 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=7 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=2 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Buprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	2.580 ratio Standard Deviation 0.9662	2.738 ratio Standard Deviation 0.5104	3.456 ratio Standard Deviation 0.9296	3.379 ratio Standard Deviation 0.9182	2.837 ratio Standard Deviation 0.8660	3.573 ratio Standard Deviation 0.5660	—

PRIMARY outcome

Timeframe: Days 1-28, 85-113

Population: PK population of participants with data at both timepoints

Accumulation index in terms of Cmax calculated as ratio of Cmax Injection 4/ Cmax Injection 1.

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=11 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=12 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=11 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=10 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=11 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=7 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Buprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	1.380 ratio Standard Deviation 0.4610	1.560 ratio Standard Deviation 0.5322	1.766 ratio Standard Deviation 0.5407	1.729 ratio Standard Deviation 0.6106	1.559 ratio Standard Deviation 0.2642	1.908 ratio Standard Deviation 0.4411	—

PRIMARY outcome

Timeframe: Days 85-113, 141-169

Population: PK population

Apparent clearance at steady-state (CLss/F) = Dose / AUCtau (tau was 28 days).

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6 Injection 4	85.543 L/hour Standard Deviation 34.6133	85.043 L/hour Standard Deviation 21.9189	105.155 L/hour Standard Deviation 23.4377	87.404 L/hour Standard Deviation 21.0436	105.390 L/hour Standard Deviation 29.3714	80.860 L/hour Standard Deviation 15.8555	—
Buprenorphine PK: Apparent Clearance at Steady-State (CLss/F) Following Injections 4 and 6 Injection 6	—	—	—	—	77.749 L/hour Standard Deviation 8.3342	79.777 L/hour	—

PRIMARY outcome

Timeframe: Days 85-113

Population: PK population of participants whose data met requirements.

Area under plasma concentration time curve from time zero of Injection 4 extrapolated to infinity; calculated for Injection 4 (last injection) in subjects not participating in PET imaging sub-study only as: (AUC0-∞ was reported if the coefficient of determination R2 was at least 0.8 and the extrapolated area is less than 25%). A minimum of 5 data points was required. AUC up to the last measurable concentration (AUClast) was calculated by using the linear trapezoidal rule.

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=2 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=1 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Buprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 (AUC0-∞)	2280.295 hr*ng/mL Standard Deviation 17.4444	3521.376 hr*ng/mL	—	—	—	—	—

PRIMARY outcome

Timeframe: Days 85-113

Population: PK population of participants whose data met requirements.

The terminal phase half life calculated for Injection 4 in subjects not participating in PET imaging sub-study. The t1/2 was reported only if the coefficient of determination R2 was at least 0.8.

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=2 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=1 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Buprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4	550.329 hours Standard Deviation 36.7325	138.238 hours	—	—	—	—	—

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

% Fluctuation was defined as the degree of fluctuation of norbuprenorphine plasma concentrations calculated as (Cmax-Cmin)/Cavg\*100, expressed as a percentage. Cmax=maximum plasma concentration Cmin=minimum plasma concentration Cavg = average plasma concentration Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Norbuprenorphine PK: % Fluctuation Plateau: Injection 1	577.952 % of average concentration Standard Deviation 119.5038	475.800 % of average concentration Standard Deviation 149.9103	504.540 % of average concentration Standard Deviation 170.1714	403.009 % of average concentration Standard Deviation 115.9346	407.217 % of average concentration Standard Deviation 160.6071	354.764 % of average concentration Standard Deviation 136.5715	—
Norbuprenorphine PK: % Fluctuation Sublingual Period	69.798 % of average concentration Standard Deviation 21.5137	94.132 % of average concentration Standard Deviation 43.7842	79.225 % of average concentration Standard Deviation 19.2173	82.834 % of average concentration Standard Deviation 29.0182	89.832 % of average concentration Standard Deviation 31.3881	71.213 % of average concentration Standard Deviation 18.7721	—
Norbuprenorphine PK: % Fluctuation Plateau: Injection 4	114.801 % of average concentration Standard Deviation 33.7254	127.106 % of average concentration Standard Deviation 64.0505	110.567 % of average concentration Standard Deviation 42.0264	77.455 % of average concentration Standard Deviation 24.7664	101.898 % of average concentration Standard Deviation 28.8808	83.579 % of average concentration Standard Deviation 18.6265	—
Norbuprenorphine PK: % Fluctuation Plateau: Injection 6	—	—	—	—	91.763 % of average concentration	242.246 % of average concentration	—
Norbuprenorphine PK: % Fluctuation Overall: Injection 1	612.998 % of average concentration Standard Deviation 141.7474	502.856 % of average concentration Standard Deviation 101.2508	685.962 % of average concentration Standard Deviation 195.9687	497.361 % of average concentration Standard Deviation 138.6539	609.481 % of average concentration Standard Deviation 145.8650	468.074 % of average concentration Standard Deviation 186.0526	—
Norbuprenorphine PK: % Fluctuation Overall: Injection 4	128.273 % of average concentration Standard Deviation 31.6391	131.080 % of average concentration Standard Deviation 57.4294	127.005 % of average concentration Standard Deviation 37.8487	95.960 % of average concentration Standard Deviation 18.6296	131.650 % of average concentration Standard Deviation 43.6260	102.192 % of average concentration Standard Deviation 12.2405	—
Norbuprenorphine PK: % Fluctuation Overall: Injection 6	—	—	—	—	94.048 % of average concentration Standard Deviation 7.4553	—	—

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Sublingual Period (0-24 hours)	42.536 hr*ng/mL Standard Deviation 17.9975	72.339 hr*ng/mL Standard Deviation 35.1371	134.739 hr*ng/mL Standard Deviation 40.4214	49.312 hr*ng/mL Standard Deviation 22.6050	65.558 hr*ng/mL Standard Deviation 25.0632	98.407 hr*ng/mL Standard Deviation 81.7085	—
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Initial Burst: Injection 1 (0-48 hours)	60.834 hr*ng/mL Standard Deviation 27.8301	98.705 hr*ng/mL Standard Deviation 54.0709	180.685 hr*ng/mL Standard Deviation 53.1546	69.878 hr*ng/mL Standard Deviation 26.1289	131.277 hr*ng/mL Standard Deviation 82.0351	148.016 hr*ng/mL Standard Deviation 97.0872	—
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Initial Burst: Injection 4 (0-48 hours)	15.435 hr*ng/mL Standard Deviation 8.0734	29.401 hr*ng/mL Standard Deviation 16.3007	50.185 hr*ng/mL Standard Deviation 19.6558	30.755 hr*ng/mL Standard Deviation 11.0344	45.941 hr*ng/mL Standard Deviation 24.8979	101.888 hr*ng/mL Standard Deviation 39.8768	—
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Initial Burst: Injection 6 (0-48 hours)	—	—	—	—	59.352 hr*ng/mL Standard Deviation 2.2741	90.719 hr*ng/mL	—
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Plateau: Injection 1 (2-28 days)	122.265 hr*ng/mL Standard Deviation 43.4215	209.679 hr*ng/mL Standard Deviation 85.5994	384.101 hr*ng/mL Standard Deviation 133.4394	197.483 hr*ng/mL Standard Deviation 59.5501	295.342 hr*ng/mL Standard Deviation 142.3582	513.577 hr*ng/mL Standard Deviation 322.8520	—
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Plateau: Injection 4 (2-28 days)	166.360 hr*ng/mL Standard Deviation 82.1264	523.076 hr*ng/mL Standard Deviation 431.7284	519.103 hr*ng/mL Standard Deviation 236.8835	410.621 hr*ng/mL Standard Deviation 146.1564	550.225 hr*ng/mL Standard Deviation 215.6699	1208.505 hr*ng/mL Standard Deviation 463.9637	—
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Plateau: Injection 6 (2-28 days)	—	—	—	—	537.212 hr*ng/mL	592.199 hr*ng/mL	—
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Overall: Injection 1 (0-24 hours)	32.465 hr*ng/mL Standard Deviation 14.2953	52.878 hr*ng/mL Standard Deviation 28.0773	99.040 hr*ng/mL Standard Deviation 30.8899	37.446 hr*ng/mL Standard Deviation 15.9959	68.660 hr*ng/mL Standard Deviation 38.8033	80.525 hr*ng/mL Standard Deviation 51.3662	—
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Overall: Injection 1 (0-28 days)	181.912 hr*ng/mL Standard Deviation 81.6100	343.357 hr*ng/mL Standard Deviation 150.5029	541.539 hr*ng/mL Standard Deviation 176.5176	261.745 hr*ng/mL Standard Deviation 81.3672	426.283 hr*ng/mL Standard Deviation 224.4167	688.487 hr*ng/mL Standard Deviation 429.8748	—
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Overall: Injection 4 (0-24 hours)	6.274 hr*ng/mL Standard Deviation 2.7973	15.199 hr*ng/mL Standard Deviation 11.7793	22.870 hr*ng/mL Standard Deviation 9.3521	13.807 hr*ng/mL Standard Deviation 5.3021	16.301 hr*ng/mL Standard Deviation 6.4778	43.722 hr*ng/mL Standard Deviation 16.4542	—
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Overall: Injection 4 (0-28 days)	182.405 hr*ng/mL Standard Deviation 91.5308	557.707 hr*ng/mL Standard Deviation 471.2095	570.958 hr*ng/mL Standard Deviation 254.4439	452.892 hr*ng/mL Standard Deviation 152.6941	673.245 hr*ng/mL Standard Deviation 167.1460	658.609 hr*ng/mL Standard Deviation 159.7954	—
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Overall: Injection 6 (0-24 hours)	—	—	—	—	—	37.093 hr*ng/mL	—
Norbuprenorphine PK: Area Under Plasma Concentration Time Curves (AUC) Overall: Injection 6 (0-28 days)	—	—	—	—	814.570 hr*ng/mL Standard Deviation 306.2799	—	—

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Norbuprenorphine PK: Average Plasma Concentration (Cavg) Sublingual Period	1.772 ng/mL Standard Deviation 0.7499	3.014 ng/mL Standard Deviation 1.4640	5.614 ng/mL Standard Deviation 1.6842	2.055 ng/mL Standard Deviation 0.9419	2.732 ng/mL Standard Deviation 1.0443	4.100 ng/mL Standard Deviation 3.4045	—
Norbuprenorphine PK: Average Plasma Concentration (Cavg) Plateau: Injection 1	0.196 ng/mL Standard Deviation 0.0696	0.336 ng/mL Standard Deviation 0.1372	0.616 ng/mL Standard Deviation 0.2138	0.316 ng/mL Standard Deviation 0.0954	0.473 ng/mL Standard Deviation 0.2281	0.823 ng/mL Standard Deviation 0.5174	—
Norbuprenorphine PK: Average Plasma Concentration (Cavg) Plateau: Injection 4	0.267 ng/mL Standard Deviation 0.1316	0.838 ng/mL Standard Deviation 0.6919	0.832 ng/mL Standard Deviation 0.3796	0.658 ng/mL Standard Deviation 0.2342	0.882 ng/mL Standard Deviation 0.3456	1.937 ng/mL Standard Deviation 0.7435	—
Norbuprenorphine PK: Average Plasma Concentration (Cavg) Plateau: Injection 6	—	—	—	—	0.861 ng/mL	0.949 ng/mL	—
Norbuprenorphine PK: Average Plasma Concentration (Cavg) Overall: Injection 1	0.271 ng/mL Standard Deviation 0.1214	0.511 ng/mL Standard Deviation 0.2240	0.806 ng/mL Standard Deviation 0.2627	0.390 ng/mL Standard Deviation 0.1211	0.634 ng/mL Standard Deviation 0.3340	1.025 ng/mL Standard Deviation 0.6397	—
Norbuprenorphine PK: Average Plasma Concentration (Cavg) Overall: Injection 4	0.271 ng/mL Standard Deviation 0.1362	0.830 ng/mL Standard Deviation 0.7012	0.850 ng/mL Standard Deviation 0.3786	0.674 ng/mL Standard Deviation 0.2272	1.002 ng/mL Standard Deviation 0.2487	0.980 ng/mL Standard Deviation 0.2378	—
Norbuprenorphine PK: Average Plasma Concentration (Cavg) Overall: Injection 6	—	—	—	—	1.212 ng/mL Standard Deviation 0.4558	—	—

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Overall: Injection 1	1.698 ng/mL Standard Deviation 0.7748	2.753 ng/mL Standard Deviation 1.4051	5,572 ng/mL Standard Deviation 1.9291	1.977 ng/mL Standard Deviation 0.7880	3.989 ng/mL Standard Deviation 2.3167	4.555 ng/mL Standard Deviation 3.1010	—
Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Overall: Injection 4	0.474 ng/mL Standard Deviation 0.2849	1.431 ng/mL Standard Deviation 1.1652	1.456 ng/mL Standard Deviation 0.4572	0.929 ng/mL Standard Deviation 0.3058	1.539 ng/mL Standard Deviation 0.6406	2.769 ng/mL Standard Deviation 1.2538	—
Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Sublingual Period (0-24 hours)	2.559 ng/mL Standard Deviation 1.0590	4.941 ng/mL Standard Deviation 2.5414	8.515 ng/mL Standard Deviation 2.3854	3.268 ng/mL Standard Deviation 1.6946	5.268 ng/mL Standard Deviation 1.9934	5.820 ng/mL Standard Deviation 4.7007	—
Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Initial Burst: Injection 1 (0-48 hours)	1.674 ng/mL Standard Deviation 0.7498	2.704 ng/mL Standard Deviation 1.3861	5.335 ng/mL Standard Deviation 1.7751	1.965 ng/mL Standard Deviation 0.7884	3.878 ng/mL Standard Deviation 2.1658	4.496 ng/mL Standard Deviation 3.0242	—
Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Initial Burst: Injection 4 (0-48 hours)	0.462 ng/mL Standard Deviation 0.2894	0.966 ng/mL Standard Deviation 0.5829	1.343 ng/mL Standard Deviation 0.4299	0.799 ng/mL Standard Deviation 0.2673	1.305 ng/mL Standard Deviation 0.5998	2.769 ng/mL Standard Deviation 1.2538	—
Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Initial Burst: Injection 6 (0-48 hours)	—	—	—	—	1.885 ng/mL Standard Deviation 0.6152	2.620 ng/mL	—
Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Plateau: Injection 1 (2-28 days)	1.165 ng/mL Standard Deviation 0.5506	1.904 ng/mL Standard Deviation 1.0984	3.201 ng/mL Standard Deviation 1.1802	1.320 ng/mL Standard Deviation 0.4278	2.203 ng/mL Standard Deviation 1.4464	3.212 ng/mL Standard Deviation 2.8810	—
Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Plateau: Injection 4 (2-28 days)	0.464 ng/mL Standard Deviation 0.2903	1.423 ng/mL Standard Deviation 1.1714	1.387 ng/mL Standard Deviation 0.4635	0.926 ng/mL Standard Deviation 0.3107	1.420 ng/mL Standard Deviation 0.7152	2.710 ng/mL Standard Deviation 1.1727	—
Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Plateau: Injection 6 (2-28 days)	—	—	—	—	1.885 ng/mL Standard Deviation 0.6152	2.620 ng/mL	—
Norbuprenorphine PK: Maximum Observed Plasma Concentration (Cmax) Overall: Injection 6	—	—	—	—	1.885 ng/mL Standard Deviation 0.6152	2.620 ng/mL	—

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Sublingual Period (0-24 hours)	1.361 ng/mL Standard Deviation 0.6010	2.342 ng/mL Standard Deviation 1.2494	4.287 ng/mL Standard Deviation 1.3351	1.582 ng/mL Standard Deviation 0.7554	2.482 ng/mL Standard Deviation 1.1788	2.923 ng/mL Standard Deviation 2.1949	—
Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Plateau: Injection 1 (2-28 days)	0.057 ng/mL Standard Deviation 0.0202	0.099 ng/mL Standard Deviation 0.0447	0.162 ng/mL Standard Deviation 0.0827	0.119 ng/mL Standard Deviation 0.0592	0.177 ng/mL Standard Deviation 0.0919	0.258 ng/mL Standard Deviation 0.1289	—
Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Plateau: Injection 4 (2-28 days)	0.165 ng/mL Standard Deviation 0.0708	0.432 ng/mL Standard Deviation 0.4181	0.548 ng/mL Standard Deviation 0.2119	0.439 ng/mL Standard Deviation 0.1550	0.587 ng/mL Standard Deviation 0.3165	1.234 ng/mL Standard Deviation 0.5279	—
Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Plateau: Injection 6 (2-28 days)	—	—	—	—	0.895 ng/mL Standard Deviation 0.3323	0.321 ng/mL	—
Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Overall: Injection 1	0.057 ng/mL Standard Deviation 0.0202	0.098 ng/mL Standard Deviation 0.0441	0.162 ng/mL Standard Deviation 0.0827	0.152 ng/mL Standard Deviation 0.1427	0.177 ng/mL Standard Deviation 0.0919	0.301 ng/mL Standard Deviation 0.2180	—
Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Overall: Injection 4	0.125 ng/mL Standard Deviation 0.0539	0.327 ng/mL Standard Deviation 0.2592	0.461 ng/mL Standard Deviation 0.2292	0.349 ng/mL Standard Deviation 0.1609	0.459 ng/mL Standard Deviation 0.2191	0.982 ng/mL Standard Deviation 0.3281	—
Norbuprenorphine PK: Minimum Observed Plasma Concentration (Cmin) Overall: Injection 6	—	—	—	—	0.728 ng/mL Standard Deviation 0.0962	0.281 ng/mL	—

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

The swing of norbuprenorphine plasma concentrations calculated as (Cmax-Cmin)/Cmin within the dosing interval. Cmax=maximum plasma concentration Cmin=minimum plasma concentration Results are reported across three timeframes: * Sublingual Period (Day -1 dose of SUBUTEX): a steady-state reading. * Plateau Parameters (Days 3-29 relative to RBP-6000 injections 1, 4 and 6) * Overall Parameters (Days 1-29 relative to RBP-6000 injections 1, 4 and 6) The PK sampling schedule was * hour 0 (predose) on days -7 to -1, * hours 0.5, 1,2,4,6, 8,12, 24 post-dose on Day -1 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672 post injections 1 and 4 * hours 0 (pre-dose) 1, 2, 4, 6, 8, 12, 20, 24, 25, 26, 28, 30, 32, 36, 44, 48, 144, 192, 240, 312, 384, 456, 528, 600, 672, 846, 1008, 1200, 1344 post injection 6

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Norbuprenorphine PK: Swing of Plasma Concentrations Plateau: Injection 4	180.340 percentage of Cmin Standard Deviation 82.9960	289.316 percentage of Cmin Standard Deviation 271.1318	171.673 percentage of Cmin Standard Deviation 98.3404	121.682 percentage of Cmin Standard Deviation 62.5967	151.990 percentage of Cmin Standard Deviation 82.8360	118.215 percentage of Cmin Standard Deviation 42.3788	—
Norbuprenorphine PK: Swing of Plasma Concentrations Plateau: Injection 1	1993.328 percentage of Cmin Standard Deviation 1002.6237	1871.238 percentage of Cmin Standard Deviation 933.9815	2531.386 percentage of Cmin Standard Deviation 1775.8060	1188.490 percentage of Cmin Standard Deviation 491.1526	1210.967 percentage of Cmin Standard Deviation 874.2858	1250.370 percentage of Cmin Standard Deviation 866.1860	—
Norbuprenorphine PK: Swing of Plasma Concentrations Sublingual Period	93.472 percentage of Cmin Standard Deviation 33.4835	130.823 percentage of Cmin Standard Deviation 74.2916	102.059 percentage of Cmin Standard Deviation 29.6116	109.416 percentage of Cmin Standard Deviation 42.1913	124.601 percentage of Cmin Standard Deviation 45.9786	101.558 percentage of Cmin Standard Deviation 38.5511	—
Norbuprenorphine PK: Swing of Plasma Concentrations Plateau: Injection 6	—	—	—	—	112.503 percentage of Cmin Standard Deviation 10.1733	716.199 percentage of Cmin	—
Norbuprenorphine PK: Swing of Plasma Concentrations Overall: Injection 1	2903.100 percentage of Cmin Standard Deviation 1102.0127	2812.484 percentage of Cmin Standard Deviation 1305.9088	4477.582 percentage of Cmin Standard Deviation 3470.4282	1776.276 percentage of Cmin Standard Deviation 923.9753	2355.099 percentage of Cmin Standard Deviation 1345.4616	2116.996 percentage of Cmin Standard Deviation 2015.7199	—
Norbuprenorphine PK: Swing of Plasma Concentrations Overall: Injection 4	322.876 percentage of Cmin Standard Deviation 297.9631	379.301 percentage of Cmin Standard Deviation 371.3835	265.586 percentage of Cmin Standard Deviation 132.0434	186.942 percentage of Cmin Standard Deviation 65.4013	272.260 percentage of Cmin Standard Deviation 139.1806	173.090 percentage of Cmin Standard Deviation 51.8058	—
Norbuprenorphine PK: Swing of Plasma Concentrations Overall: Injection 6	—	—	—	—	155.577 percentage of Cmin Standard Deviation 50.7422	832.384 percentage of Cmin	—

PRIMARY outcome

Timeframe: Day -1, Days 1-29, 85-113, 141-197

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Sublingual Period (0-24 hours)	2.000 hours Interval 0.5 to 4.0	1.017 hours Interval 0.5 to 2.0	1.000 hours Interval 0.5 to 23.58	2.000 hours Interval 0.5 to 12.0	2.000 hours Interval 1.0 to 23.67	2.000 hours Interval 1.0 to 4.0	—
Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Initial Burst: Injection 1 (0-48 hours)	8.000 hours Interval 1.0 to 48.0	6.000 hours Interval 1.0 to 48.0	4.000 hours Interval 1.0 to 30.0	12.000 hours Interval 2.0 to 30.0	6.000 hours Interval 1.0 to 30.0	4.000 hours Interval 1.0 to 36.0	—
Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Initial Burst: Injection 4 (0-48 hours)	48.000 hours Interval 1.0 to 48.07	48.000 hours Interval 4.0 to 48.0	48.000 hours Interval 6.0 to 48.1	39.000 hours Interval 8.0 to 48.03	24.000 hours Interval 4.0 to 48.0	12.000 hours Interval 6.0 to 48.0	—
Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Initial Burst: Injection 6 (0-48 hours)	—	—	—	—	48.000 hours Interval 48.0 to 48.0	48.000 hours Interval 48.0 to 48.0	—
Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Plateau: Injection 1 (2-28 days)	48.000 hours Interval 48.0 to 48.0	48.000 hours Interval 48.0 to 457.15	48.000 hours Interval 48.0 to 48.1	48.000 hours Interval 48.0 to 48.07	48.000 hours Interval 48.0 to 48.07	48.000 hours Interval 48.0 to 48.0	—
Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Plateau: Injection 4 (2-28 days)	48.000 hours Interval 48.0 to 408.52	96.883 hours Interval 48.0 to 604.77	48.100 hours Interval 48.0 to 456.8	182.808 hours Interval 48.0 to 629.07	167.017 hours Interval 48.0 to 459.0	303.133 hours Interval 48.0 to 436.75	—
Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Plateau: Injection 6 (2-28 days)	—	—	—	—	48.000 hours Interval 48.0 to 48.0	48.000 hours Interval 48.0 to 48.0	—
Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Overall: Injection 1 (0-28 days)	8.000 hours Interval 0.0 to 48.0	6.000 hours Interval 0.0 to 457.15	2.525 hours Interval 0.0 to 30.0	6.000 hours Interval 0.0 to 30.0	4.000 hours Interval 0.0 to 30.0	4.000 hours Interval 0.0 to 36.0	—
Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Overall: Injection 4 (0-28 days)	48.000 hours Interval 1.0 to 408.52	48.000 hours Interval 4.0 to 604.77	48.000 hours Interval 6.0 to 456.8	182.808 hours Interval 8.0 to 629.07	30.067 hours Interval 4.0 to 459.0	12.000 hours Interval 6.0 to 48.0	—
Norbuprenorphine PK: Time to Maximum Buprenorphine Plasma Concentration (Tmax) Overall: Injection 6 (0-28 days)	—	—	—	—	48.000 hours Interval 48.0 to 48.0	48.000 hours Interval 48.0 to 48.0	—

PRIMARY outcome

Timeframe: Days 1-28, 85-113

Population: PK population of participants with data at both timepoints

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=8 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=9 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=9 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=8 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=7 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=2 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Norbuprenorphine PK: Accumulation Index in Terms of Area Under the Curve (Rac(AUC))	1.071 ratio Standard Deviation 0.4044	1.924 ratio Standard Deviation 1.9274	1.147 ratio Standard Deviation 0.5899	1.709 ratio Standard Deviation 0.4088	1.711 ratio Standard Deviation 0.5931	1.247 ratio Standard Deviation 0.6737	—

PRIMARY outcome

Timeframe: Days 1-28, 85-113

Population: PK population of participants with data at both timepoints

Accumulation index in terms of Cmax calculated as ratio of Cmax Injection 4/ Cmax Injection 1.

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=11 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=12 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=11 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=10 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=11 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=7 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Norbuprenorphine PK: Accumulation Index in Terms of Maximum Observed Plasma Drug Concentration (Rac(Cmax))	0.300 ratio Standard Deviation 0.1294	0.697 ratio Standard Deviation 0.9077	0.272 ratio Standard Deviation 0.1131	0.548 ratio Standard Deviation 0.2978	0.445 ratio Standard Deviation 0.2231	0.730 ratio Standard Deviation 0.5830	—

PRIMARY outcome

Timeframe: Days 85-113, 141-197

Population: PK population of participants whose data met requirements.

Area under plasma concentration time curve from time zero of Injection 4 extrapolated to infinity; calculated for Injection 4 and 6 (last injection) in subjects not participating in PET imaging sub-study only as: (AUC0-∞ was reported if the coefficient of determination R2 was at least 0.8 and the extrapolated area is less than 25%). A minimum of 5 data points was required. AUC up to the last measurable concentration (AUClast) was calculated by using the linear trapezoidal rule.

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Norbuprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 and 6 (AUC0-∞) Overall: Injection 4 (0-28 days)	499.733 hr*ng/mL Standard Deviation 391.9606	1583.219 hr*ng/mL Standard Deviation 1471.7341	639.892 hr*ng/mL Standard Deviation 135.9113	—	1472.769 hr*ng/mL	—	—
Norbuprenorphine PK: Area Under Plasma Concentration Time Curve From Time Zero Of Injection 4 and 6 (AUC0-∞) Overall: Injection 6 (0-28 days)	—	—	—	—	—	737.097 hr*ng/mL	—

PRIMARY outcome

Timeframe: Days 85-113, 141-197

Population: PK population of participants whose data met requirements.

The terminal phase half life calculated for Injection 4 in subjects not participating in PET imaging sub-study. The t1/2 was reported only if the coefficient of determination R2 was at least 0.8.

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Norbuprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4 Overall: Injection 4 (0-28 days)	405.325 hours Standard Deviation 47.4883	241.914 hours Standard Deviation 114.8553	334.080 hours Standard Deviation 48.0676	—	310.879 hours	—	—
Norbuprenorphine PK: Terminal Phase Half Life (t1/2) Calculated For Injection 4 Overall: Injection 6 (0-28 days)	—	—	—	—	—	158.840 hours	—

SECONDARY outcome

Timeframe: Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141

Population: The pharmacodynamic (PD) population included subjects in Cohorts 1 - 6 who were dosed with RBP 6000 and had at least 1 post-dose value of the PD parameter.

COWS is an 11-item instrument used to assess symptoms of opioid withdrawal (Wesson et al., 1999). The score is the sum of the responses for a total range of 0-48. The COWS is commonly used by clinicians treating patients with buprenorphine to monitor the severity of withdrawal. COWS scores below 5 are considered not indicative of withdrawal. Scores from 5 to 12 are considered mild withdrawal; from 13 to 24 moderate withdrawal; 25 to 36 moderate/severe withdrawal, and 37-48 severe withdrawal. Each participant was to be assessed by the same qualified and trained individuals throughout the course of the study as much as possible. Baseline was defined as the peak (maximum) value from screening to study Day -13 pre-SUBUTEX dose. The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing and reported as change from baseline values. Negative change from baseline values indicate a lessening of withdrawal symptoms.

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6 Baseline (observed values)	17.6 units on a scale Standard Deviation 3.18	17.7 units on a scale Standard Deviation 3.22	20.4 units on a scale Standard Deviation 4.42	16.2 units on a scale Standard Deviation 2.91	17.9 units on a scale Standard Deviation 3.65	16.7 units on a scale Standard Deviation 2.33	—
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6 Day -1	-16.53 units on a scale Standard Deviation 3.335	-16.33 units on a scale Standard Deviation 4.152	-19.33 units on a scale Standard Deviation 4.670	-15.50 units on a scale Standard Deviation 2.324	-16.80 units on a scale Standard Deviation 3.986	-15.93 units on a scale Standard Deviation 2.056	—
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6 Day 1	-16.67 units on a scale Standard Deviation 3.155	-16.73 units on a scale Standard Deviation 3.788	-19.27 units on a scale Standard Deviation 4.891	-15.60 units on a scale Standard Deviation 2.720	-16.87 units on a scale Standard Deviation 3.563	-16.36 units on a scale Standard Deviation 2.341	—
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6 Day 29	-16.80 units on a scale Standard Deviation 2.908	-16.79 units on a scale Standard Deviation 3.262	-19.92 units on a scale Standard Deviation 4.663	-15.77 units on a scale Standard Deviation 3.059	-16.71 units on a scale Standard Deviation 3.989	-16.91 units on a scale Standard Deviation 2.548	—
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6 Day 57	-17.75 units on a scale Standard Deviation 3.108	-16.62 units on a scale Standard Deviation 3.776	-18.91 units on a scale Standard Deviation 4.253	-16.08 units on a scale Standard Deviation 2.937	-17.62 units on a scale Standard Deviation 3.453	-17.00 units on a scale Standard Deviation 2.449	—
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6 Day 85	-18.09 units on a scale Standard Deviation 3.015	-17.08 units on a scale Standard Deviation 3.895	-19.55 units on a scale Standard Deviation 4.059	-16.10 units on a scale Standard Deviation 2.998	-18.00 units on a scale Standard Deviation 3.873	-16.00 units on a scale Standard Deviation 2.828	—
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Prior to Injections 1, 2, 3, 4 and 6 Day 141	—	—	—	—	-19.67 units on a scale Standard Deviation 4.041	-18.00 units on a scale Standard Deviation 4.243	—

SECONDARY outcome

Timeframe: Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141

Population: The pharmacodynamic (PD) population included subjects in Cohorts 1 - 6 who were dosed with RBP 6000 and had at least 1 post-dose value of the PD parameter.

The Subjective Opiate Withdrawal Scale (SOWS) contains 16 symptoms whose intensity the participant rates on a scale of 0 (not at all) to 4 (extremely) for a full scale of 0 (no withdrawal symptoms) to 64 (extreme withdrawal symptoms). Baseline was defined as the peak (maximum) value from screening to study Day -13 pre-SUBUTEX dose. The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing and reported as change from baseline values. Negative change from baseline values indicate a lessening of withdrawal symptoms.

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6 Baseline (observed values)	40.2 units on a scale Standard Deviation 11.14	47.8 units on a scale Standard Deviation 14.65	45.1 units on a scale Standard Deviation 11.89	42.7 units on a scale Standard Deviation 13.80	42.1 units on a scale Standard Deviation 15.41	43.9 units on a scale Standard Deviation 16.20	—
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6 Day 57	-39.50 units on a scale Standard Deviation 11.844	-46.07 units on a scale Standard Deviation 16.717	-43.09 units on a scale Standard Deviation 11.631	-39.50 units on a scale Standard Deviation 13.945	-38.85 units on a scale Standard Deviation 15.486	-49.20 units on a scale Standard Deviation 12.770	—
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6 Day -1	-38.07 units on a scale Standard Deviation 11.145	-45.20 units on a scale Standard Deviation 16.794	-43.40 units on a scale Standard Deviation 12.385	-40.67 units on a scale Standard Deviation 13.563	-39.47 units on a scale Standard Deviation 16.048	-42.71 units on a scale Standard Deviation 17.117	—
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6 Day 1	-38.73 units on a scale Standard Deviation 11.285	-45.60 units on a scale Standard Deviation 16.106	-43.47 units on a scale Standard Deviation 12.489	-40.80 units on a scale Standard Deviation 13.624	-39.67 units on a scale Standard Deviation 15.041	-42.57 units on a scale Standard Deviation 16.603	—
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6 Day 29	-38.20 units on a scale Standard Deviation 12.616	-45.64 units on a scale Standard Deviation 16.832	-44.15 units on a scale Standard Deviation 11.689	-40.62 units on a scale Standard Deviation 13.997	-39.64 units on a scale Standard Deviation 15.979	-46.00 units on a scale Standard Deviation 15.205	—
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6 Day 85	-38.36 units on a scale Standard Deviation 11.595	-45.58 units on a scale Standard Deviation 16.654	-43.82 units on a scale Standard Deviation 11.763	-41.60 units on a scale Standard Deviation 14.819	-41.27 units on a scale Standard Deviation 15.691	-51.71 units on a scale Standard Deviation 13.793	—
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Prior to Injections 1, 2, 3, 4 and 6 Day 141	—	—	—	—	-45.67 units on a scale Standard Deviation 5.132	-59.50 units on a scale Standard Deviation 6.364	—

SECONDARY outcome

Timeframe: Baseline (screening to Day -13), Days -1, 1, 29, 57, 85 141

Population: The pharmacodynamic (PD) population included subjects in Cohorts 1 - 6 who were dosed with RBP 6000 and had at least 1 post-dose value of the PD parameter.

The Total Score was the sum of 10 questions regarding cravings each ranging from 0 (no craving) - 10 (extreme craving) for a total range from 0 (no cravings") to 100 ("most intense craving I have ever had"). Baseline was defined as the peak (maximum) value from screening to study Day -13 pre-SUBUTEX dose. The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing and reported as change from baseline values. Negative change from baseline values indicate a lessening of craving symptoms.

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6 Baseline (observed values)	85.6 units on a scale Standard Deviation 9.98	89.7 units on a scale Standard Deviation 10.13	87.2 units on a scale Standard Deviation 10.41	86.0 units on a scale Standard Deviation 7.67	85.1 units on a scale Standard Deviation 12.64	87.4 units on a scale Standard Deviation 11.56	—
Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6 Day 85	-84.91 units on a scale Standard Deviation 12.136	-84.92 units on a scale Standard Deviation 13.507	-86.55 units on a scale Standard Deviation 11.725	-85.70 units on a scale Standard Deviation 6.848	-89.27 units on a scale Standard Deviation 7.157	-87.14 units on a scale Standard Deviation 11.668	—
Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6 Day -1	-84.00 units on a scale Standard Deviation 10.569	-86.93 units on a scale Standard Deviation 14.255	-84.53 units on a scale Standard Deviation 11.141	-83.33 units on a scale Standard Deviation 8.449	-82.07 units on a scale Standard Deviation 12.975	-85.21 units on a scale Standard Deviation 11.088	—
Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6 Day 1	-84.47 units on a scale Standard Deviation 10.569	-88.20 units on a scale Standard Deviation 11.027	-84.40 units on a scale Standard Deviation 11.451	-83.73 units on a scale Standard Deviation 8.293	-83.00 units on a scale Standard Deviation 12.689	-85.36 units on a scale Standard Deviation 11.263	—
Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6 Day 29	-81.73 units on a scale Standard Deviation 15.975	-85.00 units on a scale Standard Deviation 12.247	-85.31 units on a scale Standard Deviation 11.272	-83.46 units on a scale Standard Deviation 8.771	-82.36 units on a scale Standard Deviation 14.836	-88.45 units on a scale Standard Deviation 10.377	—
Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6 Day 57	-84.42 units on a scale Standard Deviation 11.437	-86.64 units on a scale Standard Deviation 11.167	-86.36 units on a scale Standard Deviation 11.792	-82.08 units on a scale Standard Deviation 9.229	-83.85 units on a scale Standard Deviation 13.459	-88.10 units on a scale Standard Deviation 10.482	—
Change From Baseline in the Clinical Opioid Craving Visual Analog Scale (VAS) Total Score Prior to Injections 1, 2, 3, 4 and 6 Day 141	—	—	—	—	-85.33 units on a scale Standard Deviation 1.528	-85.00 units on a scale Standard Deviation 4.243	—

SECONDARY outcome

Timeframe: Baseline (screening Day -15), Days 1, 7, 29, 57, 85, 141

Population: The pharmacodynamic (PD) population included subjects in Cohorts 1 - 6 who were dosed with RBP 6000 and had at least 1 post-dose value of the PD parameter. One participant from Group 2 did not have a baseline evaluation.

The CGI-S is a 7-item scale completed by the clinician used to rate the severity of symptoms. The total range is 1 (normal, not at all ill) to 7 (most extremely ill). Baseline was defined as value from screening (Day -13). The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing (not applicable for Day 7) and reported as change from baseline values. Negative change from baseline values indicate a lessening of the severity of symptoms.

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=14 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141 Baseline (observed values)	4.3 units on a scale Standard Deviation 0.49	4.3 units on a scale Standard Deviation 0.61	4.4 units on a scale Standard Deviation 0.51	4.6 units on a scale Standard Deviation 0.51	4.7 units on a scale Standard Deviation 0.72	4.6 units on a scale Standard Deviation 0.51	—
Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141 Day 7	-1.00 units on a scale Standard Deviation 1.095	-0.50 units on a scale Standard Deviation 0.527	-1.25 units on a scale Standard Deviation 0.965	—	—	—	—
Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141 Day 1	0.00 units on a scale Standard Deviation 0.000	0.00 units on a scale Standard Deviation 0.000	0.13 units on a scale Standard Deviation 0.352	0.00 units on a scale Standard Deviation 0.000	0.00 units on a scale Standard Deviation 0.000	0.00 units on a scale Standard Deviation 0.000	—
Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141 Day 29	-1.40 units on a scale Standard Deviation 1.056	-1.00 units on a scale Standard Deviation 1.038	-1.23 units on a scale Standard Deviation 0.927	-1.38 units on a scale Standard Deviation 0.961	-1.64 units on a scale Standard Deviation 0.929	-1.91 units on a scale Standard Deviation 1.044	—
Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141 Day 57	-1.75 units on a scale Standard Deviation 1.055	-1.29 units on a scale Standard Deviation 1.204	-1.91 units on a scale Standard Deviation 1.221	-1.83 units on a scale Standard Deviation 1.115	-2.00 units on a scale Standard Deviation 1.000	-2.50 units on a scale Standard Deviation 1.269	—
Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141 Day 85	-1.82 units on a scale Standard Deviation 0.751	-1.83 units on a scale Standard Deviation 1.115	-2.18 units on a scale Standard Deviation 0.874	-2.30 units on a scale Standard Deviation 1.160	-2.64 units on a scale Standard Deviation 1.120	-2.86 units on a scale Standard Deviation 1.345	—
Change From Baseline in the Clinical Global Impression Severity (CGI-S) Scale on Days 1, 7, 29, 57, 85 and 141 Day 141	—	—	—	—	-3.00 units on a scale Standard Deviation 1.000	-2.00 units on a scale Standard Deviation 2.828	—

SECONDARY outcome

Timeframe: Baseline (Day 1), Days 7, 29, 57, 85, 141

The CGI-I is a 7-item scale completed by the clinician used to rate their impression of how much the participant has improved over a baseline state. The total range is 1 (very much improved) to 7 (very much worse). Baseline was defined as value from Day 1. The baseline score is reported as the mean of observed values. Other measurements were taken prior to dosing (not applicable for Day 7) and reported as change from baseline values. Negative change from baseline values indicate an improvement.

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=13 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141 Day 85	-2.18 units on a scale Standard Deviation 0.603	-2.00 units on a scale Standard Deviation 0.953	-2.73 units on a scale Standard Deviation 0.467	-2.60 units on a scale Standard Deviation 0.699	-2.73 units on a scale Standard Deviation 0.647	-2.57 units on a scale Standard Deviation 0.787	—
Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141 Baseline (observed values)	4.0 units on a scale Standard Deviation 0.00	4.1 units on a scale Standard Deviation 0.26	4.0 units on a scale Standard Deviation 0.00	4.0 units on a scale Standard Deviation 0.00	4.0 units on a scale Standard Deviation 0.00	4.0 units on a scale Standard Deviation 0.00	—
Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141 Day 7	-1.00 units on a scale Standard Deviation 1.095	-0.73 units on a scale Standard Deviation 0.905	-1.42 units on a scale Standard Deviation 1.084	—	—	—	—
Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141 Day 29	-1.67 units on a scale Standard Deviation 0.976	-1.07 units on a scale Standard Deviation 1.072	-1.77 units on a scale Standard Deviation 1.092	-1.69 units on a scale Standard Deviation 0.947	02.07 units on a scale Standard Deviation 0.616	-2.27 units on a scale Standard Deviation 1.191	—
Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141 Day 57	-2.08 units on a scale Standard Deviation 0.793	-1.79 units on a scale Standard Deviation 0.975	-2.36 units on a scale Standard Deviation 0.809	-2.17 units on a scale Standard Deviation 0.937	-2.15 units on a scale Standard Deviation 0.801	-2.40 units on a scale Standard Deviation 0.966	—
Change From Baseline in the Clinical Global Impression Improvement (CGI-I) Scale on Days 7, 29, 57, 85 and 141 Day 141	—	—	—	—	-2.67 units on a scale Standard Deviation 0.577	-2.50 units on a scale Standard Deviation 0.707	—

SECONDARY outcome

Timeframe: Screening (summary of lifetime), Screening (last 6 months), Day 65, Day 113, End of Study (up to day 365)

Population: PD population

The scale used in the C-SSRS is a continuous variable ranging from 0 (no suicidal ideation present) to 5 (active ideation with specific plan and intent). Only participants with suicidal ideation (scale of 1-5) are reported. 1=desire to be dead to 5=active ideation with specific plan and intent.

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Columbia Suicide Severity Rating Scale (C-SSRS): Severity Screening (summary of lifetime)	1.0 units on a scale	—	1.8 units on a scale Standard Deviation 0.45	2.0 units on a scale Standard Deviation 1.41	1.0 units on a scale	1.3 units on a scale Standard Deviation 0.58	—
Columbia Suicide Severity Rating Scale (C-SSRS): Severity Screening (last 6 months)	—	—	—	—	—	1.0 units on a scale	—
Columbia Suicide Severity Rating Scale (C-SSRS): Severity Day 65	—	—	—	—	1.0 units on a scale	1.0 units on a scale	—
Columbia Suicide Severity Rating Scale (C-SSRS): Severity Day 113	—	1.0 units on a scale	—	—	—	—	—
Columbia Suicide Severity Rating Scale (C-SSRS): Severity End of study	—	—	5.0 units on a scale	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 to End of Study (up to day 365)

Population: Safety population

Urine samples were screened for the following drugs: * opiates * cocaine * amphetamines * methadone * cannabinoids * barbiturates * buprenorphine. Buprenorphine was only included in the urine drug screen at screening and Day -14 to determine if the subject had used any buprenorphine-containing products prior to the start of SUBUTEX SL tablet dosing. * benzodiazepines * methamphetamine * phencyclidine Urine drug screens were run every day when the participant was an inpatient; every 2-3 days when the participant was an outpatient. Drug screens were run less often for those participants in the PET substudy.

Outcome measures

Outcome measures
Measure	SUBUTEX Only n=15 Participants Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 Participants Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 Participants Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=14 Participants Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Percentage of Urine Drug Screen Samples Negative for Opioids	41.2 percentage of total urine drug samples Standard Deviation 32.89	42.0 percentage of total urine drug samples Standard Deviation 35.43	54.6 percentage of total urine drug samples Standard Deviation 23.98	49.9 percentage of total urine drug samples Standard Deviation 25.53	41.6 percentage of total urine drug samples Standard Deviation 27.68	64.9 percentage of total urine drug samples Standard Deviation 23.56	—

Adverse Events

SUBUTEX Only

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Group 1 (8 mg) RBP-6000: 50 mg

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Group 2 (12 mg) RBP-6000: 100 mg

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Group 3 (24 mg) RBP-6000: 200 mg

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Group 4 (8 mg) RBP-6000: 100 mg

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Group 5 (14 mg) RBP-6000: 200 mg

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Group 6 (8-24 mg) RBP-6000: 300 mg

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SUBUTEX Only n=35 participants at risk Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 participants at risk Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 participants at risk Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 participants at risk Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 participants at risk Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=15 participants at risk Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 112 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg n=14 participants at risk Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Infections and infestations Lobar pneumonia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Nervous system disorders Encephalopathy	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Psychiatric disorders Personality disorder	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Psychiatric disorders Suicidal ideation	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Pelvic inflammatory disease	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Vaginitis bacterial	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Vascular disorders Deep vein thrombosis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316

Other adverse events

Other adverse events
Measure	SUBUTEX Only n=35 participants at risk Participants who entered the Induction/Stabalization period, were treated with SUBUTEX SL and did not continue into the Treatment period.	Group 1 (8 mg) RBP-6000: 50 mg n=15 participants at risk Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 50 mg are given at 28 day intervals.	Group 2 (12 mg) RBP-6000: 100 mg n=15 participants at risk Participants are stabilized by day -5 on Subutex 12 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals	Group 3 (24 mg) RBP-6000: 200 mg n=15 participants at risk Participants are stabilized by day -5 on Subutex 24 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 113 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 4 (8 mg) RBP-6000: 100 mg n=15 participants at risk Participants are stabilized by day -5 on Subutex 8 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 100 mg are given at 28 day intervals.	Group 5 (14 mg) RBP-6000: 200 mg n=15 participants at risk Participants are stabilized by day -5 on Subutex 14 mg. During the study, four subcutaneous (SC) injections containing RBP-6000 200 mg are given at 28 day intervals. Participants who reach Day 112 (and have received all 4 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 200 mg SC injections at 28 day intervals for an additional 6-9 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.	Group 6 (8-24 mg) RBP-6000: 300 mg n=14 participants at risk Participants are stabilized by day -5 on a Subutex between 8-24 mg. During the study, up to six subcutaneous (SC) injections containing RBP-6000 300 mg are given at 28 day intervals. Participants who reach Day 168 (and have received all 6 planned SC injections) have the option to participate in the Positron Emission Tomography (PET) Pilot substudy. In the PET Pilot sub-study participants remain on 300 mg SC injections at 28 day intervals for an additional 6 intervals until they complete an magnetic resonance imaging (MRI) and a PET scan and pharmacokinetic samples at week 1 and week 4 post injection.
Gastrointestinal disorders Gingivitis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Oral pain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Blood and lymphatic system disorders Anaemia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Blood and lymphatic system disorders Granulocytopenia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Blood and lymphatic system disorders Leukoyctosis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Blood and lymphatic system disorders Thrombocytopenia	2.9% 1/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Cardiac disorders Tachycardia	2.9% 1/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	14.3% 2/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Cardiac disorders Atrioventricular block first degree	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Cardiac disorders Sinus tachycardia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	20.0% 3/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Ear and labyrinth disorders Vertigo	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Ear and labyrinth disorders Cerumen impaction	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Ear and labyrinth disorders Ear pain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Eye disorders Conjunctival hyperaemia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Eye disorders Dry eye	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Vomiting	8.6% 3/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	26.7% 4/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	33.3% 5/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	26.7% 4/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	46.7% 7/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	35.7% 5/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Constipation	17.1% 6/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	46.7% 7/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	53.3% 8/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	53.3% 8/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	40.0% 6/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	53.3% 8/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	28.6% 4/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Nausea	5.7% 2/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	20.0% 3/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	40.0% 6/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	14.3% 2/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Toothache	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	20.0% 3/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	14.3% 2/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Abdominal pain upper	2.9% 1/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Diarrhoea	2.9% 1/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Eructation	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Abdominal pain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Dental caries	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Dry mouth	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Dyspepsia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Faeces hard	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Gastrointestinal disorders Gastritis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Drug withdrawal syndrome	34.3% 12/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	60.0% 9/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	73.3% 11/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	86.7% 13/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	86.7% 13/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	93.3% 14/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	50.0% 7/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Fatigue	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	21.4% 3/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Injection site pruritus	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	21.4% 3/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Chills	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Facial pain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Injection site erythema	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Injection site pain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Irritability	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Inflammation	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Influenza-like illness	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Injection site dermatitis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Injection site papule	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Oedema peripheral	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Pain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
General disorders Pyrexia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Hepatobiliary disorders Hepatic cyst	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Immune system disorders Seasonal allergy	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Immune system disorders Autoimmune disorder	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Upper respiratory tract infection	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	26.7% 4/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	33.3% 5/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	33.3% 5/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	20.0% 3/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	42.9% 6/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Gastroenteritis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	20.0% 3/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Nasopharyngitis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Pharyngitis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Tinea pedis	2.9% 1/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Tooth infection	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Urinary tract infection	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Viral infection	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Bronchitis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Chlamydial infection	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Folliculitis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Gastroenteritis viral	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Hordeolum	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Infective glossitis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Onychomycosis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Otitis media	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Perirectal abscess	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Postoperative wound infection	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Tooth abscess	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Vulvovaginal candidiasis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Excoriation	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	14.3% 2/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Laceration	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	14.3% 2/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Contusion	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	20.0% 3/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Injury	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Corneal abrasion	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Muscle strain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Procedural pain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Rib fracture	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Sunburn	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Testicular injury	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Thermal burn	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Investigations Blood creatinine phosphokinase increased	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Investigations Oxygen saturation decreased	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Investigations Alanine aminotransferase increased	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Investigations Aspartate aminotransferase increased	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Investigations Blood bilirubin increased	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Investigations Blood pressure increased	5.7% 2/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Investigations Body temperature increased	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Investigations Hepatic enzyme increased	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Investigations Liver function test abnormal	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Investigations Weight decreased	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Investigations Weight increased	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Investigations White blood cell count increased	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Metabolism and nutrition disorders Hypertriglyceridemia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Metabolism and nutrition disorders Weight fluctuation	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.7% 2/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	60.0% 9/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	46.7% 7/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	40.0% 6/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	20.0% 3/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	26.7% 4/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	42.9% 6/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	20.0% 3/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid neoplasm	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Nervous system disorders Headache	22.9% 8/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	46.7% 7/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	40.0% 6/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	60.0% 9/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	46.7% 7/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	60.0% 9/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	50.0% 7/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Nervous system disorders Dizziness	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	14.3% 2/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Nervous system disorders Myoclonus	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Nervous system disorders Hypoaesthesia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Nervous system disorders Lethargy	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Nervous system disorders Migraine	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Nervous system disorders Paraesthesia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Nervous system disorders Presyncope	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Nervous system disorders Restless leg syndrome	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Nervous system disorders Somnolence	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Pregnancy, puerperium and perinatal conditions Vomiting in pregnancy	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Psychiatric disorders Anxiety	5.7% 2/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	40.0% 6/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	60.0% 9/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	33.3% 5/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	26.7% 4/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	57.1% 8/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Psychiatric disorders Abnormal dreams	5.7% 2/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	20.0% 3/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	21.4% 3/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Psychiatric disorders Insomnia	5.7% 2/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	20.0% 3/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	20.0% 3/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	21.4% 3/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Psychiatric disorders Depressed mood	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Psychiatric disorders Intentional self-injury	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Psychiatric disorders Panic attack	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Psychiatric disorders Restlessness	2.9% 1/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	20.0% 3/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Psychiatric disorders Substance-induced mood disorder	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Psychiatric disorders Substance-induced psychotic disorder	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Renal and urinary disorders Leukocyturia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Renal and urinary disorders Haematuria	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Renal and urinary disorders Pyuria	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Renal and urinary disorders Urinary hesitation	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Respiratory, thoracic and mediastinal disorders Nasal ulcer	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Night sweats	2.9% 1/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	14.3% 2/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Blister	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Acne	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Eczema asteatotic	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Erythema	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Rash	2.9% 1/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Swelling face	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Social circumstances Physical assault	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Vascular disorders Phlebitis	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	7.1% 1/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Vascular disorders Hot flush	0.00% 0/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	6.7% 1/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	13.3% 2/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Cardiac disorders Bundle branch block right	2.9% 1/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Cardiac disorders Ventricular extrasystoles	2.9% 1/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Infections and infestations Abscess limb	2.9% 1/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316
Vascular disorders Orthostatic hypertension	2.9% 1/35 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/15 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316	0.00% 0/14 • - Subutex Only Days -14 to Day -1 - Groups 1-4 (no PET substudy): Days -14 up to Day 141 - Groups 5-6 (including PET substudy): Days -14 up to Day 316

Additional Information

Global Director, Clinical Development

Indivior, Inc.

Phone: 804-379-1090

Results disclosure agreements

Principal investigator is a sponsor employee Proposed publications shall be submitted to Sponsor 30 days prior to submission for publication, and may be withheld for an additional period, up to 90 days, to allow Sponsor to file patent applications. If a multi-center publication isn't submitted for publication within 12 months of the conclusion of the Study at all sites, or is published in a shorter period, the results from the institution's site may be published individually.
Publication restrictions are in place

Restriction type: OTHER